Evaluation of a new type of nano-sized carbon monoxide donor on treating mice with experimentally induced colitis
Evaluation of a new type of nano-sized carbon monoxide donor on treating mice with experimentally induced colitis
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DOI：
10.1016/j.jconrel.2016.05.016
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发表时间：
2016-07-28
影响因子：
10.8
通讯作者：
Maruyama, Toru
中科院分区：
文献类型：
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作者：
Nagao, Saori;Taguchi, Kazuaki;Maruyama, Toru
据报道，低浓度的外源性一氧化碳（CO）可用于治疗与炎症和氧化应激相关的各种病症。然而，许多障碍使得难以在体内使用CO。其中，在高浓度下，它是有毒的，并且难以控制其在体内的传递。血红蛋白囊泡（Hemoglobin-vesicles，HbV）是一种新型的纳米级一氧化碳供体，被称为一氧化碳结合的血红蛋白囊泡（CO-HbV）。在这项研究中，我们使用实验性结肠炎模型研究了CO-HbV作为CO供体在毒性和治疗功效方面的潜力。CO-HbV的毒理学评估显示，在给予高达1400 mg Hbfkg的剂量后，没有严重的不良反应，包括死亡，临床实验室检查和组织病理学变化在28天内保持正常。然后，我们评估了CO-HbV对硫酸氯昔川钠（DSS）诱导的结肠炎模型小鼠的治疗效果。与盐水和HbV给药相比，在DSS治疗开始后3天单次给予CO-HbV显著改善了结肠炎症状、结肠组织病理学变化和存活期。此外，CO-HbV对结肠炎的治疗作用可归因于降低的中性粒细胞浸润水平、促炎细胞因子的产生和氧化损伤。有趣的是，似乎抗炎细胞因子产生的增加部分地有助于CO-HbV在结肠炎治疗中的治疗效果。CO-HbV的这些安全性和有效性特征表明，它不仅有可能用作治疗结肠炎的药物，而且还有可能用作治疗与炎症和氧化应激相关的各种其他疾病的药物。(C)© 2016 Elsevier B. V.版权所有。
Low concentrations of exogenous carbon monoxide (CO) have been reported to be useful for the treatment of various disorders related to inflammation and oxidative stress. However, a number of obstacles make it difficult to use CO in vivo. Among these are, at high concentrations, it is toxic and the fact that it is difficult to control its delivery in the body. Hemoglobin-encapsulated liposomes, Hemoglobin-vesicles (HbV), have the potential for use as a new type of nano-sized CO donor, referred to as CO-bound HbV (CO-HbV). In this study, we investigated the potential of CO-HbV as a CO donor in terms of toxicity and therapeutic efficacy using an experimental colitis model Toxicological assessments of CO-HbV showed no severe adverse effects including death, and clinical laboratory tests and histopathological changes remained normal for 28 clays after the administration of closes up to 1400 mg Hbfkg. We then evaluated the therapeutic efficacies of CO-HbV on clextran sulfate sodium (DSS)-inducal colitis model mice. A single administration of CO-HbV at 3 clays from beginning of the DSS treatment dramatically improved colitis symptoms, colonic histopathological changes and the duration of survival compared to both saline and HbV administration. In addition, the therapeutic effects of CO-HbV on colitis can be attributed to a decreased level of neutrophil infiltration, the production of pro-inflammatory cytokines and oxidative injuries. Interestingly, it appears that an increase in anti-inflammatory cytokine production contributes, in part, to therapeutic effects of CO-HbV in the treatment of colitis. These safety and efficacy profiles of CO-HbV suggest that it has the potential for use as a drug for treating, not only colitis but also a variety of other disorders associated with inflammation and oxidative stress. (C) 2016 Elsevier B.V. All rights reserved.